tbuckley/cabot-search huggingface dataset:
Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood: Combined Exposure to Seven PFAS
Authors: Katia Keglberg Hærvig, Kajsa Ugelvig Petersen, Karin Sørig Hougaard, Christian Lindh, Cecilia Høst Ramlau-Hansen, Gunnar Toft, Aleksander Giwercman, Birgit Bjerre Høyer, Esben Meulengracht Flachs, Jens Peter Bonde, Sandra Søgaard Tøttenborg
Journal: Environmental Health Perspectives (2022)

Background: Concerns remain about the human reproductive toxicity of the widespread per- and polyfluoroalkyl substances (PFAS) during early stages of development. Objectives: We examined associations between maternal plasma PFAS levels during early pregnancy and male offspring reproductive function in adulthood. Methods: The study included 864 young men (age range:18.9–21.2 y) from the Fetal Programming of Semen Quality (FEPOS) cohort established between 2017 and 2019. Plasma samples from their mothers, primarily from the first trimester, were retrieved from the Danish National Biobank and levels of 15 PFAS were measured. Seven PFAS had detectable levels above the limit of detection in &gt;80% of the samples and were included in analyses. Semen quality, testicular volume, and levels of reproductive hormones and PFAS were assessed in the young men. We used weighted quantile sum (WQS) regression to estimate the associations between combined exposure to maternal PFAS and reproductive function, and negative binomial regression to estimate the associations of single substances, while adjusting for a range of a priori–defined fetal and postnatal risk factors. Results: By a 1-unit increase in the WQS index, combined maternal PFAS exposure was associated with lower sperm concentration (−8%; 95% CI: −16%, −1%), total sperm count (−10%; 95% CI: −17%, −2%), and a higher proportion of nonprogressive and immotile sperm (5%; 95% CI: 1%, 8%) in the young men. Different PFAS contributed to the associations with varying strengths; however, perfluoroheptanoic acid was identified as the main contributor in the analyses of all three outcomes despite the low concentration. We saw no clear association between exposure to maternal PFAS and testicular volume or reproductive hormones. Discussion: In a sample of young men from the general Danish population, we observed consistent inverse associations between exposure to maternal PFAS and semen quality. The study needs to be replicated in other populations, taking combined exposure, as well as emerging short-chain PFAS, into consideration. https://doi.org/10.1289/EHP10285
Genome-wide study on 72,298 individuals in Korean biobank data for 76 traits
Authors: Kisung Nam, Jangho Kim, Seunggeun Lee
Journal: Cell Genomics (2022)

Genome-wide association studies (GWAS) on diverse ancestry groups are lacking, resulting in deficits of genetic discoveries and polygenic scores. We conducted GWAS for 76 phenotypes in Korean biobank data, namely the Korean Genome and Epidemiology Study (KoGES) (n = 72,298). Our analysis discovered 2,242 associated loci, including 122 novel associations, many of which were replicated in Biobank Japan (BBJ) GWAS. We also applied several up-to-date methods for genetic association tests to increase the power, discovering additional associations that are not identified in simple case-control GWAS. We evaluated genetic pleiotropy to investigate genes associated with multiple traits. Following meta-analysis of 32 phenotypes between KoGES and BBJ, we further identified 379 novel associations and demonstrated the improved predictive performance of polygenic risk scores by using the meta-analysis results. The summary statistics of 76 KoGES GWAS phenotypes are publicly available, contributing to a better comprehension of the genetic architecture of the East Asian population.
TP53 or Not TP53: That Is the Question
Authors: Steven D. Green, Joshua F. Zeidner
Journal: Clinical Cancer Research (2022)

Azacitidine and venetoclax are a standard first-line regimen for patients with newly diagnosed unfit acute myeloid leukemia (AML). In a pooled subset analysis, TP53-mutated AML with poor-risk cytogenetics does not appear to benefit from the addition of venetoclax to azacitidine. This has clinical implications as these patients should be preferentially treated with alternative regimens. See related article by Pollyea et al., p. 5272
Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal
Authors: Matthew B. Pomrenze, Daniel F. Cardozo Pinto, Peter A. Neumann, Pierre Llorach, Jason M. Tucciarone, Wade Morishita, Neir Eshel, Boris D. Heifets, Robert C. Malenka
Journal: Neuron (2022)
A cis-regulatory lexicon of DNA motif combinations mediating cell-type-specific gene regulation
Authors: Laura K.H. Donohue, Margaret G. Guo, Yang Zhao, Namyoung Jung, Rose T. Bussat, Daniel S. Kim, Poornima H. Neela, Laura N. Kellman, Omar S. Garcia, Robin M. Meyers, Russ B. Altman, Paul A. Khavari
Journal: Cell Genomics (2022)

Gene expression is controlled by transcription factors (TFs) that bind cognate DNA motif sequences in cis-regulatory elements (CREs). The combinations of DNA motifs acting within homeostasis and disease, however, are unclear. Gene expression, chromatin accessibility, TF footprinting, and H3K27ac-dependent DNA looping data were generated and a random-forest-based model was applied to identify 7,531 cell-type-specific cis-regulatory modules (CRMs) across 15 diploid human cell types. A co-enrichment framework within CRMs nominated 838 cell-type-specific, recurrent heterotypic DNA motif combinations (DMCs), which were functionally validated using massively parallel reporter assays. Cancer cells engaged DMCs linked to neoplasia-enabling processes operative in normal cells while also activating new DMCs only seen in the neoplastic state. This integrative approach identifies cell-type-specific cis-regulatory combinatorial DNA motifs in diverse normal and diseased human cells and represents a general framework for deciphering cis-regulatory sequence logic in gene regulation.
A brain atlas of synapse protein lifetime across the mouse lifespan
Authors: Edita Bulovaite, Zhen Qiu, Maximilian Kratschke, Adrianna Zgraj, David G. Fricker, Eleanor J. Tuck, Ragini Gokhale, Babis Koniaris, Shekib A. Jami, Paula Merino-Serrais, Elodie Husi, Lorena Mendive-Tapia, Marc Vendrell, Thomas J. O’Dell, Javier DeFelipe, Noboru H. Komiyama, Anthony Holtmaat, Erik Fransén, Seth G.N. Grant
Journal: Neuron (2022)

The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.
Glia-neuron interplay drives circadian glycosphingolipid homeostasis and structural brain plasticity
Authors: Marco Brancaccio
Journal: Neuron (2022)

Glia-neuronal interplay is critical for circadian regulation of physiology and behavior. In this issue of Neuron, Vaughen et al. identify daily variations of glycosphingolipids that depend on glia and whose disruption alters proteostasis and daily structural plasticity of Drosophila circadian circuits.
Association of Long-term Oncologic Prognosis With Minimal Access Breast Surgery vs Conventional Breast Surgery
Authors: Andi Wan, Yan Liang, Li Chen, Shushu Wang, Qiyun Shi, Wenting Yan, Xiaozhen Cao, Ling Zhong, Linjun Fan, Peng Tang, Guozhi Zhang, Siyi Xiong, Cheng Wang, Zhen Zeng, Xiujuan Wu, Jun Jiang, Xiaowei Qi, Yi Zhang
Journal: JAMA Surgery (2022)

Minimal access breast surgery (MABS) has been used in breast cancer management. However, long-term prognostic data associated with MABS vs conventional breast surgery (CBS) are lacking.
Characterizing the Language Used to Discuss Death in Family Meetings for Critically Ill Infants
Authors: Margaret H. Barlet, Mary C. Barks, Peter A. Ubel, J. Kelly Davis, Kathryn I. Pollak, Erica C. Kaye, Kevin P. Weinfurt, Monica E. Lemmon
Journal: JAMA Network Open (2022)

Communication during conversations about death is critical; however, little is known about the language clinicians and families use to discuss death.To characterize (1) the way death is discussed in family meetings between parents of critically ill infants and the clinical team and (2) how discussion of death differs between clinicians and family members.This longitudinal qualitative study took place at a single academic hospital in the southeast US. Patients were enrolled from September 2018 to September 2020, and infants were followed up longitudinally throughout their hospitalization. Participants included families of infants with neurologic conditions who were hospitalized in the intensive care unit and had a planned family meeting to discuss neurologic prognosis or starting, not starting, or discontinuing life-sustaining treatment. Family meetings were recorded, transcribed, and deidentified before being screened for discussion of death.The main outcome was the language used to reference death during family meetings between parents and clinicians. Conventional content analysis was used to analyze data.A total of 68 family meetings involving 36 parents of 24 infants were screened; 33 family meetings (49%) involving 20 parents (56%) and 13 infants (54%) included discussion of death. Most parents involved in discussion of death identified as the infant's mother (13 [65%]) and as Black (12 [60%]). Death was referenced 406 times throughout the family meetings (275 times by clinicians and 131 times by family members); the words die, death, dying, or stillborn were used 5% of the time by clinicians (13 of 275 references) and 15% of the time by family members (19 of 131 references). Four types of euphemisms used in place of die, death, dying, or stillborn were identified: (1) survival framing (eg, not live), (2) colloquialisms (eg, pass away), (3) medical jargon, including obscure technical terms (eg, code event) or talking around death with physiologic terms (eg, irrecoverable heart rate drop), and (4) pronouns without an antecedent (eg, it). The most common type of euphemism used by clinicians was medical jargon (118 of 275 references [43%]). The most common type of euphemism used by family members was colloquialism (44 of 131 references [34%]).In this qualitative study, the words die, death, dying, or stillborn were rarely used to refer to death in family meetings with clinicians. Families most often used colloquialisms to reference death, and clinicians most often used medical jargon. Future work should evaluate the effects of euphemisms on mutual understanding, shared decision-making, and clinician-family relationships.
Association Does Not Equal Causation—Does Thinking You Are Better Make You Better?
Authors: John C. Alverdy
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Phase 2 Evaluation of Neoadjuvant Intensity-Modulated Radiotherapy in Centrally Located Hepatocellular Carcinoma
Authors: Fan Wu, Bo Chen, Dezuo Dong, Weiqi Rong, Hongzhi Wang, Liming Wang, Shulian Wang, Jing Jin, Yongwen Song, Yueping Liu, Hui Fang, Yuan Tang, Ning Li, Xianggao Zhu, Yexiong Li, Weihu Wang, Jianxiong Wu
Journal: JAMA Surgery (2022)

Centrally located hepatocellular carcinoma (HCC) is a special type of HCC whose outcome is unsatisfactory when treated with surgery alone. No standard adjuvant or neoadjuvant treatment for this disease has been established that improves clinical outcomes.To evaluate the effectiveness and safety of adding neoadjuvant intensity-modulated radiotherapy (IMRT) before surgery in patients with centrally located HCC.This phase 2, single-center, single-group prospective nonrandomized controlled trial was conducted between December 16, 2014, and January 29, 2019, at the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences in Beijing, China. The last follow-up was on July 30, 2021. Patients with centrally located HCC who underwent neoadjuvant IMRT and surgery were included in the analysis.Neoadjuvant IMRT followed by hepatectomy.The primary end point was 5-year overall survival (OS). The secondary end points were tumor response to IMRT, 5-year disease-free survival (DFS), and treatment-related adverse events.Thirty-eight patients (mean [SD] age, 55.6 [9.3] years; 35 male [92.1%] individuals) completed the prescribed neoadjuvant IMRT without interruption. Radiographic tumor response to IMRT before surgery included partial response (16 [42.1%]) and stable disease (22 [57.9%]). Thirteen patients (34.2%) achieved major pathological response, of which 5 (13.2%) achieved pathologic complete response. With a median follow-up of 45.8 months, the median OS was not reached, and the OS rates were 94.6% at 1 year, 75.4% at 3 years, and 69.1% at 5 years. The median DFS was 45.8 months, and DFS rates were 70.3% at 1 year, 54.1% at 3 years, and 41.0% at 5 years. Radiotherapy-related grade 3 adverse events were observed in 3 patients (7.9%). Nineteen operative complications developed in 13 patients (34.2%), including grade I to II complications in 12 patients (31.6%) and grade IIIa complication in 1 patient (2.6%). No grade IIIb or higher operative complications were observed.Results of this trial suggest that neoadjuvant IMRT plus surgery is effective and well-tolerated in patients with centrally located HCC. These data may inform a future randomized clinical trial of this new treatment strategy.ClinicalTrials.gov Identifier: NCT02580929.
Apremilast in Recalcitrant Cutaneous Dermatomyositis
Authors: Carole Bitar, Thien Ninh, Katherine Brag, Soraya Foutouhi, Stella Radosta, Jade Meyers, Melody Baddoo, Delong Liu, Brittany Stumpf, Paul W. Harms, Nakhle S. Saba, Erin Boh
Journal: JAMA Dermatology (2022)

Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians.To study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021.Apremilast 30 mg orally twice daily was added to ongoing treatment regimens.The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0.Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P < .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39 076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.ClinicalTrials.gov Identifier: NCT03529955.
Implementation of Antenatal Lifestyle Interventions Into Routine Care
Authors: Mahnaz Bahri Khomami, Helena J. Teede, Joanne Enticott, Sharleen O’Reilly, Cate Bailey, Cheryce L. Harrison
Journal: JAMA Network Open (2022)

Importance Lifestyle interventions in pregnancy optimize gestational weight gain and improve pregnancy outcomes, with implementation recommended by the US Preventive Services Task Force. Yet, implementation research taking these efficacy trials into pragmatic translation remains limited. Objective To evaluate success factors for implementing pregnancy lifestyle interventions into antenatal care settings in a meta-analysis, using the penetration, implementation, participation, and effectiveness (PIPE) impact metric. Data Sources Data from a previous systematic review that searched across 9 databases, including MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database, were obtained, in 2 stages, up to May 6, 2020. Study Selection Randomized clinical trials reporting gestational weight gain in singleton pregnancies. Data Extraction and Synthesis The association of penetration, implementation, and participation with effectiveness of antenatal lifestyle interventions in optimizing gestational weight gain was estimated using random-effects meta-analyses. The Cochrane risk of bias tool, version 1.0, was used to assess risk of bias. Main Outcomes and Measures Penetration (reach), implementation (fidelity), participation, and effectiveness of randomized clinical trials of lifestyle interventions in pregnancy. Results Ninety-nine studies with 34 546 participants were included. Only 14 studies reported penetration of target populations. Overall, 38 studies (38.4%) had moderate fidelity, 25 (25.2%) had high fidelity, and 36 (36.4%) had unclear fidelity. Participation was reported in 84 studies (84.8%). Lifestyle interventions were associated with reducing gestational weight gain by 1.15 kg (95% CI, –1.40 to –0.91 kg). Conclusions and Relevance The findings of this systematic review and meta-analysis suggest that, despite the large body of evidence on efficacy of lifestyle interventions during pregnancy in optimizing gestational weight gain, little guidance is available to inform implementation of this evidence into practice. There is a need to better elucidate implementation outcomes in trial design alongside pragmatic implementation research to improve the health of women who are pregnant and the next generation.
Implementation of a Geriatric Trauma Clinical Pathway—Reply
Authors: Caroline Park, Kristan Staudenmayer
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Retailer Compliance With Tobacco 21 in New Jersey, 2019-2020
Authors: Mary Hrywna, Amanda Y. Kong, Christopher Ackerman, Shawna V. Hudson, Cristine D. Delnevo
Journal: JAMA Network Open (2022)

This cross-sectional study assesses retailer compliance with the Tobacco 21 law in New Jersey during 2019 and 2020.